My ninth genome of Christmas is a bit of an indulgence: the gentlemanly, diminutive Medaka fish, or Japanese rice paddy fish.When Mendel’s laws were rediscovered in the 1900s, many scientists turned to local species they could keep easily to explore this brave, new world of genetics. In America, Thomas Hunt chose the fruit fly. Scientists in Germany explored the guppy and Ginuea pigs. In England, crop plants were the focus of early genetics. In Japan, researchers turned to the tiny Medaka fish, a common addition to many of the ornamental ponds maintained in Japanese gardens.
You might think that the best chemists on earth are humans, living perhaps in Cambridge, Heidelberg, Paris, Tokyo or Shenzhen, beavering away in laboratories filled with glassware, extraction hoods and other human-made things. But then you would be discounting a multitude of bacteria that have cracked all sorts of chemistry problems over the course of their long evolution, and that still harbour secrets about how they manipulate molecules. One inventive clade of bacteria, the cyanobacteria, quite literally changed the world, and built the foundations of modern life.
When you first think of domesticated organisms, dogs might come to mind (our earliest domestication), or perhaps wheat, or cattle or rice. But you might easily overlook single-celled yeast: the key active agreement in both bread and alcohol, and a great enabler of the agricultural revolution in Europe. Wild yeast lives on fruit and seeds, and is dispersed by the wind. The earliest use of these wild organisms involved capturing them to make alcohol (wine) and to make sourdough bread rise. For the routine production of beer and bread, brewers and bakers kept cultures of ‘good’ yeast, eventually selecting for specific strains of Saccharomyces cerevisiae: a single-celled fungus that can live both in aerobic (oxygen present) and anaerobic (no oxygen) conditions.
If humans have an arch enemy, it might well be the tiny, blood-borne parasite Plasmodium falciparum. This nasty beast causes most of the malaria in sub-Saharan Africa and, together with its cousins, in many tropical zones throughout the world. It kills huge numbers of children every year, and constantly cycles through the bloodstreams of its many survivors. It has been with us since our explosive migration out of east Africa, and in fact many genetic diseases (including sickle-cell aneamia and thalassemias) are tolerated by human populations because they confer an advantage against this nasty parasite.
The humble fruit fly – Drosophila melanogaster, to be specific – has played a central role in the history of genetics and molecular biology and continues to be important in research.
Championed by the legendary Thomas Morgan at the start of the 20th Century, Drosophila provided a practical foundation for genetics – long before the discovery of DNA as vehicle for passing down heritable information through generations. Morgan and colleagues developed the concepts of ‘gene’ and ‘linkage’, and so we have ‘Morgans’ (and more commonly, centi-Morgans, cM) as the basic units of genetic maps.
The first technological innovation to radically change human society was agriculture. The ability to cultivate – rather than hunt or pick – food had a profound change on everything from our immune system to our societal structures. It encouraged specialisation, favoured robust, complex inter-generational knowledge transmission and enabled the explosive growth of this bipedal ape.
In the early 90s Svante Paabo, a charismatic, energetic innovator, made a bold proposal: that to study human origins one would do well to sequence the DNA of ancient hominids, in particular those species which had gone extinct. After all, DNA could be detected in their bones, provided they were not too old and kept dry and cold.
On the second day of christmas, my true love sent to me:
The C. elegans (worm) genome. The lowly nematode worm is probably the “newest” widespread model organism, developed by Sydney Brenner and colleagues in the 1960s at the Laboratory for Molecular Biology (LMB) in Cambridge as something between the complexity of fly and the simplicity of yeast. It was an inspired choice: you could keep the worm in the laboratory easily (it eats a lawn of bacteria, very often E. coli), and setting up crosses was easy and remarkably (and this shows how lucky Sydney is) it has completely stereotypical development. Every adult C. elegans worm has an identical number of cells (John Sulston was one of the key people to work this out who would later lead the worm and genome project). It is as if every cell has name, with one tree providing the single way of going from a genome to a collection of cells.
Inspired by a very boring train stoppage last year, I am going to add, one a day, to this of great / interesting genomes until christmas day.
On the first day of christmas, my true love sent to me:
Escherichia coli and its associated phages. This humble bacterium is one of our commensal organisms; it hangs out in our gut being, usually, useful to us. But the reason why every molecular biologists knows about this critter is that it is also the bedrock of DNA manipulation. Molecular biologists shuttle DNA from all sorts of different organisms through E. coli constantly. It is the assembly line for much of molecular biology – where you capture, grow up, extract DNA. The smell of the growth media to grow E. coli infuses all molecular biology labs. E. coli has its own parasites – phages – which are viruses that infect E.coli, and these are as useful as their bacterial host.
One of the great challenges – and opportunities – over the coming decade is the perfusion of molecular measurement, and accompanying data analysis, into general medicine. This will be nothing new for clinical genetics and other niche disciplines, but as medicine begins to mine the rich data streams from genomics, transcriptomics and metabolomics research, we will start running into some rather tricky integration problems. This is interesting both scientifically and socially, as a huge wave of technology pushes us to create clinical utility out of a confluence of molecular data, high-resolution imaging and data from continuous-sensing devices.